1. Mosaic deletion patterns of the human antibody heavy chain gene locus shown by Bayesian haplotyping
- Author
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Andrew M. Collins, Ludvig M. Sollid, Ayelet Peres, Francois Vigneault, Gur Yaari, Christopher Clouser, Pazit Polak, Ivana Mikocziova, Moriah Gidoni, Vikas Kumar Sarna, Ida Lindeman, Knut E.A. Lundin, and Omri Snir
- Subjects
0301 basic medicine ,DNA Copy Number Variations ,Genotype ,Science ,Immunoglobulin Variable Region ,General Physics and Astronomy ,Inference ,Sequence assembly ,Locus (genetics) ,02 engineering and technology ,Computational biology ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Antibody Repertoire ,Humans ,Copy-number variation ,lcsh:Science ,Alleles ,Multidisciplinary ,Haplotype ,Bayes Theorem ,General Chemistry ,021001 nanoscience & nanotechnology ,030104 developmental biology ,ComputingMethodologies_PATTERNRECOGNITION ,Haplotypes ,IGHD ,lcsh:Q ,Immunoglobulin Heavy Chains ,0210 nano-technology ,IGHV@ - Abstract
Analysis of antibody repertoires by high-throughput sequencing is of major importance in understanding adaptive immune responses. Our knowledge of variations in the genomic loci encoding immunoglobulin genes is incomplete, resulting in conflicting VDJ gene assignments and biased genotype and haplotype inference. Haplotypes can be inferred using IGHJ6 heterozygosity, observed in one third of the people. Here, we propose a robust novel method for determining VDJ haplotypes by adapting a Bayesian framework. Our method extends haplotype inference to IGHD- and IGHV-based analysis, enabling inference of deletions and copy number variations in the entire population. To test this method, we generated a multi-individual data set of naive B-cell repertoires, and found allele usage bias, as well as a mosaic, tiled pattern of deleted IGHD and IGHV genes. The inferred haplotypes may have clinical implications for genetic disease predispositions. Our findings expand the knowledge that can be extracted from antibody repertoire sequencing data., High-throughput sequencing and analyzes of antibody repertoire provide important information on immune responses, but current methodologies are limited in sequence assembly precision and haplotype inference validity. Here the authors propose a new Bayesian haplotyping method, and attest its broad application with a large, multi-individual dataset.
- Published
- 2019